The prospect of doing human clinical trials with stem cells to treat diseases like multiple sclerosis may be growing closer, say
scientists at the University at Buffalo and the University at Rochester, who
have developed a more precise way to isolate stem cells that will make
myelin.

Myelin is the crucial fatty material that coats neurons and
allows them to signal effectively. The inability to make myelin properly is the
cause of MS as well as rare, fatal, childhood diseases, such as Krabbe's
disease.

The research, published online and in the October issue of
Nature Biotechnology, overcomes an important barrier to the use of stem cells
from the brain in treating demyelinating diseases.

Until now, it has been
difficult to separate out the right progenitor cells the ones that will develop
into cells that make myelin, explains Fraser Sim, PhD, first and
co-corresponding author on the paper and assistant professor in the Department
of Pharmacology and Toxicology in the UB School of Medicine and Biomedical
Sciences; he did much of the work while he was a researcher at
Rochester.

"Characterizing and isolating the exact cells to use in stem
cell therapy is one key to ultimately having success," said Sim. "You need to
have the right cells in hand before you can even think about getting to a
clinical trial to treat people. This is a significant step."

Sim and
Rochester graduate student Crystal McClain ran extensive analyses looking at
gene activity in different types of stem cells, leading to the conclusion that
stem cells carrying a protein known as CD140a on their surface seemed to be most
likely to become oligodendrocytes the type of brain cell that makes
myelin.

The UB and Rochester scientists then injected the cells into the
brains of mice that were born without the ability to make myelin. Twelve weeks
later, the cells had become oligodendrocytes and had coated more than 40 percent
of the brain's neurons with myelin a four-fold improvement over the team's
previous results published in Cell Stem Cell and Nature Medicine.

"These
cells are our best candidates right now for someday helping patients with M.S.,
or children with fatal hereditary myelin disorders," said Steven Goldman, MD,
PhD, co-author, the leader of the team and professor and chair of the Department
of Neurology at the University of Rochester Medical Center. "These cells migrate
more effectively throughout the brain, and they myelinate other cells more
quickly and more efficiently than any other cells assessed thus far. Now we
finally have a cell type that we think is safe and effective enough to propose
for clinical trials."

An eventual treatment of a disease like M.S. might
involve injecting stem cells to create myelin in the brains of
patients.

"Another approach," says Sim, "might involve using certain
medications to turn on these cells already present in the brains of patients and
thereby create new myelin. The use of the new techniques described in this work
will permit us to better understand how human cells behave in the brain and help
us predict which medications may be successful in the treatment of myelin
loss."

The new approach may also be applicable to Krabbe's Disease, Sim
says, which also involves the breakdown of myelin. Sim, who came to UB in 2009,
is actively collaborating on related work with researchers at the Hunter James
Kelly Research Institute, a partnership between UB and the Hunter's Hope
Foundation and located in UB's New York State Center of Excellence in
Bioinformatics and Life Sciences.